title: Altered xanthine oxidase and N-acetyltransferase activity in obese children.
abstract: OBJECTIVE
  It is well established that oxidative and conjugative enzyme activity differs between obese and healthy-weight adults. However, the effect of obesity on drug metabolism in children has not been studied extensively. This study examined whether obese and healthy-weight children vary with respect to oxidative enzyme activity of CYP1A2, xanthine oxidase (XO) and conjugative enzyme activity of N-acetyltransferase 2 (NAT2).
  
  
  METHODS
  In vivo CYP1A2, XO and NAT2 activity was assessed in obese (n= 9) and lean (n= 16) children between the ages of 6-10 years using caffeine (118.3 ml Coca Cola®) as probe. Urine samples were collected in 2-h increments over 8 h. Caffeine and metabolites were measured using LC/MS, and urinary metabolic ratios were determined based on reported methods.
  
  
  RESULTS
  Sixteen healthy-weight and nine obese children were evaluated. XO activity was elevated in paediatric obese volunteers compared with non-obese paediatric volunteers (XO metabolic ratio of 0.7 ± 0.06 vs. 0.6 ± 0.06, respectively, 95% CI 0.046, 0.154, P < 0.001). NAT2 activity was fivefold higher in the obese (1 ± 0.4) as compared with non-obese children (0.2 ± 0.1), 95% CI 0.26, 1.34, P < 0.05. However, no difference was observed in CYP1A2 activity between the groups (95% CI -2.72, 0.12, P > 0.05).
  
  
  CONCLUSIONS
  This study provides evidence that obese children have elevated XO and NAT2 enzyme activity when compared with healthy-weight controls. Further studies are needed to determine how this may impact the efficacy of therapeutic agents that may undergo metabolism by these enzymes.
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard ST SE, 7-115C WDH Minneapolis, MN, USA.
authors.forename: Manoj S
authors.initials: MS
authors.lastname: Chiney
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Schwarzenberg
authors.forename: L'aurelle A
authors.initials: LA
authors.lastname: Johnson
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D015415:Biomarkers; D001835:Body Weight; D002110:Caffeine / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D015233:Models, Statistical; D009765:Obesity / Q000201:enzymology*; D014969:Xanthine Oxidase / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2; D014969:Xanthine Oxidase; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human